crossing96/oncoscreening huggingface dataset:
Expression and antigenicity of survivin, an inhibitor of apoptosis family member, in bladder cancer: implications for specific immunotherapy.	OBJECTIVES: To assess the expression of survivin in transitional cell carcinoma of the bladder and to study whether survivin is a transitional cell carcinoma-specific antigen that could be a target for immunotherapy. Survivin, an inhibitor of apoptosis family member, has been reported to be expressed in various cancers but not in normal adult tissues. METHODS: Immunohistochemical staining for survivin and human leukocyte antigen (HLA) class I was performed on specimens from 88 patients who underwent transurethral resection and radical cystectomy. To determine whether survivin was recognized as a tumor antigen by the host immune system, we assessed anti-survivin antibodies in the sera of 52 patients and 18 healthy volunteers with an enzyme-linked immunosorbent assay using recombinant survivin. RESULTS: Survivin and HLA class I were expressed in 77 (87.5%) and 59 (67.0%) of the 88 bladder cancer specimens, respectively, and 56 (63.6%) expressed both survivin and HLA class I. The absorbance values of anti-survivin antibodies in patients with bladder cancer were significantly greater than those in the healthy volunteers. A relationship was found between the level of serum anti-survivin antibodies and the staining intensity of survivin in the specimen. CONCLUSIONS: Survivin is expressed in carcinoma of the bladder with high sensitivity. It is suggested that survivin is presented on HLA class I molecules of antigen-presenting cells in 64% of patients with bladder cancer. Therapeutic targeting of survivin in bladder cancer is a future possibility.	bladder
Visualization of tumor cell extravasation.	In cancer the blood-borne spread of tumor cells leads to the formation of secondary tumors at distant loci, whereby the extravasation of tumor cells is a prerequisite step during hematogenous metastasis. In regard to the fate of endothelial cells located at the site of tumor cell infiltration, tumor cell-endothelial interactions were analyzed using an in vitro real-time model. This model shows the complete sequence of the transmigration process and gave new insights into the complex and dynamic cell-cell and cell-matrix interactions which occur during tumor cell transmigration across the endothelial barrier. An in vitro real-time apoptosis assay permits the distinction between apoptotic cell death from necrotic cell death. This model indicates that transmigration of tumor cell clusters derived from the invasive human bladder carcinoma cell line T24 irreversibly damages the endothelial cells by inducing apoptosis at the site of tumor cell infiltration. It is postulated here that apoptosis induction facilitates the removal of detached endothelial cells, thereby forestalling a local inflammatory response which might be detrimental to extravasating tumor cells.	bladder
Malignant paraganglioma of the urinary bladder: Immunohistochemical study of prognostic indicators.	Using various immunohistochemical markers, the objective of our study was to assess whether correlation exists between growth potential of paraganglioma (pheochromocytoma) cells and formation of metastasis. The patient was a 28-yr-old man who presented with intermittent episodes of gross hematuria due to a mass in the urinary bladder. He had no constitutional symptoms to suggest paraganglioma. Histologic, immunohistochemical, and electron microscopic investigation of the surgically removed tissue proved that the tumor was a malignant paraganglioma with metastases in the regional lymph nodes. The immunohistochemical tests were not supportive of high cell proliferation index, indicating that metastases can develop in the absence of rapid multiplication of the tumor cells. Abnormalities in vascular architecture and marked expression of VEGF in the tumor cells may be regarded as prognostic signs to predict the formation of metastases.	bladder
Adjuvant chemotherapy for invasive bladder cancer (individual patient data).	BACKGROUND: Controversy exists as to whether adjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite a number of randomised controlled trials. OBJECTIVES: To evaluate the effect of adjuvant chemotherapy in invasive bladder cancer. We conducted a systematic review and meta-analysis of updated individual patient data from all available randomised controlled trials comparing local treatment plus adjuvant chemotherapy versus the same local treatment alone. SEARCH STRATEGY: MEDLINE and Cancerlit searches were supplemented with information from registers and hand searching meeting proceedings and also by discussion with relevant trialists and organisations. They have been regularly updated until September 2004. SELECTION CRITERIA: Trials that aimed to randomise patients with biopsy proven invasive (i.e. clinical stage T2-T4a) transitional cell carcinoma of the bladder to receive local definitive treatment with or without adjuvant chemotherapy were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We collected, validated and re-analysed updated data on all randomised patients from all available randomised trials, including 491 patients from 6 RCTs. For all outcomes, we obtained overall pooled hazard ratios using the fixed effects model. To explore the potential impact of trial design, we pre-planned analyses that grouped trials by important aspects of their design that might influence the treatment effect. To investigate any differences in effect by pre-defined patient sub-groups, we used a stratified logrank analysis on the primary endpoint of survival. MAIN RESULTS: Analyses were based on 491 patients from six trials, representing 90% of all patients randomised in cisplatin-based combination chemotherapy trials and 66% of patients from all eligible trials. The power of this meta-analysis is clearly limited. The overall hazard ratio for survival of 0.75 (95%CI 0.60-0.96, p=0.019) suggests a 25% relative reduction in the risk of death for chemotherapy compared to that on control. Cox regression suggests that small imbalances in patient characteristics do not bias the results in favour of chemotherapy. However, the impact of trials that stopped early, of patients not receiving allocated treatments or not receiving salvage chemotherapy is less clear. AUTHORS' CONCLUSIONS: This IPD meta-analysis provides the best evidence currently available on the role of adjuvant chemotherapy for invasive bladder cancer. However, at present there is insufficient evidence on which to reliably base treatment decisions. These results highlight the urgent need for further research into the use of adjuvant chemotherapy. The results of appropriately sized randomised trials, such as the ongoing EORTC-30994 trial are needed before any definitive conclusions can be drawn.	bladder
Elevated prostaglandin E2 level via cPLA2--COX-2--mPGES-1 pathway involved in bladder carcinogenesis induced by terephthalic acid-calculi in Wistar rats.	To investigate the prostaglandin E2 (PGE2) biosynthetic mechanism in bladder carcinogenesis, we established Wistar rat model of bladder papilloma and transitional cell carcinoma (TCC) induced by 5% terephthalic acid (TPA) treatment. Then, the mRNA level of cytosolic phospholipase A2 (cPLA2), cyclooxygenases (COX)-1 and -2, membrane-bound PGE2 synthases (mPGES)-1 and -2 was detected using reverse transcription polymerase chain reaction (RT-PCR). Immunoblotting was applied to detect the expression of COX-2 protein. Proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry. In addition, the level of PGE2 was measured by radioimmunoassay (RIA). Bladder papilloma (100%, 8/8) was examined in rats after 24-week treatment, and bladder TCC (80%, 16/20) was found after 48-week treatment. Histopathological changes were not found in control group rats. The incidence of bladder papilloma and TCC in test group was significantly higher than that in control group (P<0.01). The mRNA levels of cPLA2, COX-2 and mPGES-1 in the bladder papilloma and TCC were significantly higher than those in normal bladder (P<0.01), while the mRNA levels of COX-1 and mPGES-2 in TCC were unchanged compared with normal bladder. Bladder TCC exhibited a substantial expression of COX-2 protein. On the contrary, normal bladder tissue barely expresses COX-2 protein. PCNA labeling index (LI) and the level of PGE2 in bladder papilloma are much higher than those in normal bladder (P<0.01), but lower than those in bladder TCC (P<0.05). In conclusion, increasing PGE2 level via cPLA2--COX-2--mPGES-1 pathway may play an important role in rat bladder carcinogenesis. PGE2 may be a biomarker for the development of bladder TCC. cPLA2 and mPGES-1 may be targets for development of novel chemoprevention strategies for bladder TCC.	bladder
Microarray analyses in bladder cancer cells: inhibition of hTERT expression down-regulates EGFR.	The human telomerase reverse transcriptase (hTERT) contributes to the immortal phenotype of the majority of cancers. Targeting hTERT by transfection with antisense oligonucleotides (AS-ODNs) induced immediate growth inhibition in human bladder cancer (BCa) cells. The molecular basis of the antiproliferative capacity of hTERT AS-ODNs was investigated by oligonucleotide microarray analyses and was compared to effects caused by siRNA-mediated knock-down of hTERT in EJ28 BCa cells. Two different AS-ODNs -- both down-regulated the expression of hTERT -- changed the expression of different genes mainly involved in stress response (including EGR1, ATF3 and GDF15), but without an association to telomerase function. This indicates that the immediate growth inhibition was caused, at least in part, by off-target effects. In comparison to that the blockade of the expression of hTERT using 2 different siRNAs was accompanied by the down-regulation of the oncogenes FOS-like antigen 1 (FOSL1) and epidermal growth factor receptor (EGFR), known to be overexpressed in BCa. We show here for the first time that repression of the hTERT transcript number decreased the expression of EGFR both at the mRNA and protein levels, suggesting a potential new function of hTERT in the regulation of EGFR-stimulated proliferation. Furthermore, the suppression of hTERT by siRNAs caused an enhancement of the antiproliferative capacity of the chemotherapeutics mitomycin C and cisplatin. The results presented herein may support the hypothesis that hTERT promotes the growth of tumor cells by mechanisms independent from telomere lengthening. The detailed clarification of these processes will shed light on the question, whether telomerase inhibitors might constitute suitable anticancer tools.	bladder
A novel method for gene expression mapping of metastatic competence in human bladder cancer.	"Expression profiling by DNA microarray analysis has provided insights into molecular alterations that underpin cancer progression and metastasis. Although differential expression of microarray-defined probes can be related to numerical or structural chromosomal alterations, it is unclear if such changes are also clustered in distinct chromosomes or genomic regions and whether chromosomal alterations always reflect changes in gene expression. Here we apply the dChip algorithm and a novel technique to test the hypothesis that expression changes occurring as a function of tumor progression and metastasis are nonrandomly distributed. Expression profiling of a human xenograft model of lung metastasis phenotype indicates that chromosomes 2, 11, and 20 contain higher percentages of differentially expressed genes (P < .05). Furthermore, we show that a number of differentially expressed probes mapped to chromosome 17q, defining the existence of an expression ""hot spot"" corresponding to an area of gain determined by comparative genomic hybridization (CGH). Interestingly, other areas of gains detected by CGH were not associated with expression hot spots. In summary, we show that gene expression changes during bladder cancer lung metastasis occur nonrandomly in specific chromosomes and intrachromosomal locations."	bladder
The effect of repeat transurethral resection on recurrence and progression rates in patients with T1 tumors of the bladder who received intravesical mitomycin: a prospective, randomized clinical trial.	PURPOSE: We compared the outcomes of repeat transurethral resection plus intravesical mitomycin C with initial transurethral resection of bladder plus intravesical MMC in patients with newly diagnosed pT1 transitional cell carcinoma of the bladder in terms of recurrence, progression and overall survival. MATERIALS AND METHODS: Of 148 newly diagnosed patients with T1 bladder cancer 142 were prospectively randomized in 2 groups between January 2001 and January 2005. A total of 74 patients underwent second TURB and received adjuvant MMC intravesically (group 1) and 68 patients received adjuvant MMC following the initial TURB (group 2). All repeat TURB operations were performed 2 to 6 weeks following initial TURB. Patients with incomplete resection, Cis or muscle invasive disease were excluded from study. The first dose of mitomycin C (40 mg per week for a total of 8 weeks) was instilled intravesically in all patients during the first 24 hours after the last surgery. RESULTS: Mean followup was 31.5 months (range 6 to 48) with no difference between the 2 groups. The rate of recurrence-free survival was 86.35% (SE 0.4%), 77.67% and 68.72% in group 1, and 47.08%, 42.31% and 37.01% in group 2 for the first, second and third year, respectively (overall 74.32% vs 36.76%, log rank 0.0001). Recurrence was observed in 19 of the 74 (25.68%) patients in group 1 and in 43 of the 68 (63.24%) patients in group 2. Ten of the 19 (52.63%) patients in group 1 and 35 of the 43 (81.39%) patients in group 2 had recurrence within 12 months. Recurrence was observed in 17.6%, 25% and 60% of patients with G1, G2 and G3 tumors, respectively, in group 1. The same rates for group 2 were 25%, 64% and 90%. The RFS rate was significantly worse in the high grade group (G2 and G3) (p <0.001). Progression was observed at 4.05% for group 1 compared to 11.76% for group 2 (log rank 0.0974). OS was 91.89% and 89.71% in group 1 and 2, respectively (log rank 0.732). CONCLUSIONS: The high recurrence rate in patients who did not undergo ReTUR is due to a high residual tumor rate following initial TURB. The benefit of ReTUR is especially true for high grade tumors. Since intravesical MMC was present in both groups, this study has shown that intravesical chemotherapy does not compensate for inadequate resection. Progression does not seem to be affected by ReTUR although there was a trend favoring the ReTUR group. We recommend ReTUR for patients with primary high grade T1 disease to achieve better recurrence-free survival.	bladder
Recurrent transitional cell carcinoma in a scrotal abscess.	We discuss a case of recurrent transitional cell carcinoma to the scrotum 5 years after cystectomy, along with its postoperative management and implications.	bladder
Induction of G2/M arrest and inhibition of cyclooxygenase-2 activity by curcumin in human bladder cancer T24 cells.	Curcumin, a polyphenol compound derived from Curcuma longa Linn, has been recognized as a promising anti-cancer drug due to its multiple properties including anti-inflammatory, anti-oxidant and anti-carcinogenic activities. To elucidate the mechanisms by which curcumin inhibits human bladder carcinoma T24 cell proliferation, we tested the effects of curcumin on specific cell cycle pathways and on the expression of cyclooxygenases (COXs). Curcumin inhibited the growth of T24 cells and induced G2/M arrest in a concentration-dependent manner, effects associated with the down-regulation of cyclin A and up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1). However, other G2/M regulatory molecules, such as cyclin A, Cdc2, Cdk2, Wee1 and Cdc25C, were not modulated by curcumin treatment. Furthermore, curcumin decreased the levels of COX-2 mRNA and protein expression without significant changes in the levels of COX-1, which correlated with a decrease in prostaglandin E2 (PGE2) synthesis. These observations suggest that curcumin may have therapeutic potential for bladder cancer patients.	bladder
Microscopic hematuria as a predictive factor for detecting bladder cancer at cystoscopy in women with irritative voiding symptoms.	OBJECTIVE: The purpose of this study was to assess microscopic hematuria as a predictive factor for detecting bladder cancer at cystoscopy in women with irritative voiding symptoms. STUDY DESIGN: We conducted a retrospective cohort analysis of women with irritative voiding symptoms who presented for urodynamic testing and cystoscopy. Irritative voiding symptoms were defined as urgency, urge incontinence, frequency, dysuria, and/or nocturia. Patient demographics, risk factors for bladder cancer, presence of microscopic hematuria, urodynamic findings, and cystoscopy and biopsy results were recorded. RESULTS: Of 735 patients with irritative voiding symptoms, 264 (35.9%) had microscopic hematuria and 471 (64.1%) had no hematuria. Bladder cancer was detected in 3 women, for an overall detection rate of 0.4%. Microscopic hematuria, urgency, frequency, dysuria, nocturia, age, and tobacco use were not significantly associated with bladder cancer. CONCLUSION: In this cohort of women with irritative voiding symptoms, microscopic hematuria was not predictive for bladder cancer.	bladder
"Implants of noninvasive papillary urothelial carcinoma in peritoneum and ileocolonic neobladder: support for ""seed and soil"" hypothesis of bladder recurrence."	"OBJECTIVES: To explore the underlying mechanism of tumor regrowth in cases of noninvasive urothelial carcinoma that recur in unusual anatomic locations. METHODS: The pathology files of our institution and the consult service of one of us were searched for cases of noninvasive nonmetastatic urothelial carcinoma with involvement of unusual anatomic sites. Cases in which the mode of spread included direct spread to the adjacent tissue and lymphovascular metastases were excluded. Medical history, including presenting symptoms, and follow-up data were obtained. RESULTS: Two cases of noninvasive urothelial carcinoma were identified. One had presented as an implant in the peritoneal investment of the bladder dome and the other as multiple implants growing on the benign surface of the colonic mucosa of an orthotopic neobladder distant from the anastomosis site. Both cases had initially presented as noninvasive papillary urothelial carcinoma of the renal pelvis. Although the urinary bladder was free of neoplastic changes at nephroureterectomy, both patients also developed several papillary tumors within the bladder shortly after the removal of the kidney. CONCLUSIONS: After clinicopathologic correlation, the mode of tumor spread in these cases was best explained by the ""seeding/implantation"" theory. The urothelial tumor cells in each of these cases demonstrated the ability to implant themselves not only in the urothelium of the bladder but also in the colonic mucosa of a constructed neobladder and on the peritoneal surface."	bladder
Review pathology in a diagnostic bladder cancer trial: effect of patient risk category.	OBJECTIVES: Bladder cancer pathologic features are a continuous spectrum from benign to invasive lesions, causing diagnostic difficulties. Review pathology might be an answer, but appears to be of limited value. We studied the effect of patients' risk profile on the value of review pathology. METHODS: We used three Phase III multicenter studies that assessed the value of hexaminolevulinate fluorescence cystoscopy on diagnosis and management. Two studies (Europe and United States) included patients at high risk of carcinoma in situ (CIS), the third study (Europe) included all patients at risk of bladder cancer. Tumors and biopsies were examined by a local and review pathologist. RESULTS: The percentage of patients with CIS was high in the first two studies (20.6% and 15.9%) compared with the epidemiologic data (7.9%) and the third study (7.8%). The numbers of patients (specimens) in the three studies were 209 (927), 277 (986), and 142 (553). Overall conformity for both grade and stage was between 50.5% and 56.6%, comparable to published data. Although conformity was best in the high-risk study, this was predominantly because of the better conformity in low-risk tumors. Conformity in Stage T1, CIS, and invasive tumors was low. The results from Europe and the United States were comparable, although the local pathologist in the United States tended to overstage or overgrade. CONCLUSIONS: Although histologic conformity was greater in the high-risk patient population, this was mainly a result of pTa tumors. The diagnosis of pT1, CIS, and invasiveness appears difficult. Because these tumors significantly influence therapy, review pathology in patients at high risk or suspicious for high risk should be considered.	bladder
Association of PAX5 expression with clinical outcome in patients with TaT1 transitional cell carcinoma of the bladder.	OBJECTIVES: To assess the frequency and intensity of PAX5 gene messenger ribonucleic acid (mRNA) expression in TaT1 bladder cancer tissue, as well as its correlation with clinicopathologic variables and patient outcome. METHODS: The RNA expression of PAX5 was evaluated with reverse transcriptase polymerase chain reaction in the tumor tissue of 75 patients with stage TaT1 bladder cancer treated with transurethral resection. Patients were observed with cystoscopy and urinary cytologic evaluation. The association between PAX5 expression and clinicopathologic variables and patient outcome was evaluated. Benign urothelium from 8 patients with benign prostatic hyperplasia was obtained. These patients were used as a control group. RESULTS: PAX5 expression was found in 62 patients with bladder cancer (82.7%) but in no patient from the control group. High PAX5 expression (greater than 0.2) was confirmed in 19 patients (25.3%). No significant relationship was observed between quantity of PAX5 expression and clinicopathologic variables. The 3-year recurrence-free and progression-free survival rates in highly positive patients were 13.2% and 71.6%, compared with 40.6% and 92.8%, respectively, in patients with weak or negative expression (log-rank test, P = 0.0075, P = 0.022). Multivariate Cox proportional hazard model analysis identified PAX5 expression as an independent predictor of tumor recurrence. CONCLUSIONS: PAX5 gene expression is a frequent finding in superficial transitional cell carcinoma of the bladder. High levels of PAX5 are associated with poorer recurrence-free and progression-free survival rates. Moreover, PAX5 expression was found to be an independent prognostic factor for recurrence-free survival by a multivariate analysis.	bladder